Caudal Clonidine in Day-Care Paediatric Surgery

Summary Weevaluated theanalgesic efficacy, hemodynamic and respiratory safety of clonidinewhen added to bupivacaine for caudal block. Forty children undergoing inguinal hernia repair were randomly given caudal injection with 0.75 ml.kg -1 of bupivacaine (0.25%) and clonidine 2 µg.kg -1 in Group C or 0.75 ml.kg -1 of bupivacaine (0.25%) alone in Group B after induction of anaesthesia. Postoperatively duration of analgesia, OPS score (observational pain / dis-comfort scale), Sedation score, heart rate and blood pressure were recorded. Duration of analgesia was significantly longer (p< 0.001) in Group C (10.25 hours) as compared to 4.55 hours in Group B. Bradycardia, hypotension and sedation were not observed in Group C. Theaddition of clonidine in caudal blocksprolongs postoperativepain relief in children and is safe alternative to bupivacaine alone in paediatric daycare surgeries.

Prolongation of caudal block using a single shot technique; can be achieved byaddition of various adjuvants. Epinephrinewas the earliest adjuvant drug used, during second half of 1980's. Opioids were also used but their use carried risk of respiratory depression 1 . Ketamineas an adjuvant haspotential forneurotoxic effects if inadvertently injected intrathecally 2 and neostigmine is accompanied by 30% incidence of vomiting 3 .
Clonidine, an  -2adrenergic agonist, produces analgesia without significant respiratorydepression. The analgesic action of epidurally administered clonidine is due to stimulation of descending noradrenergic medullospinalpathways inhibitingthe release of nociceptive neurotransmitters in the dorsal horn of spinal cord 4 . The analgesic effect of clonidine is more pronounced after neuraxial injection which suggests a spinalsite of action and makesthis route of administration preferable 5,6 .
We designed a prospective randomized double blind study to examinethe haemodynamicand respiratory effects of clonidine as an adjunct to bupivacaine caudal epidural analgesia and compare its analgesic efficacy with control group in which only bupivacaine was used, in paediatric day care procedures.

Methods
After informed parental consent, 40ASAI children between 1-10 years of age weighing 5-20 kg, who were scheduled to undergo inguinal herniotomy as daycare cases were admitted in the study. Children with any contraindication to caudal block or having congenital heartdisease wereexcluded from the study. No premedication was given and all surgeries were performed under general anaesthesia. Inhalational induction was done with oxygen, nitrous oxide and 8% sevoflurane delivered through Jackson Rees modification of Ayre's T-piece and face mask, with standard monitoring.After intravenouscannula insertiona PLMA (ProsealLaryngeal MaskAirway, LMAcompany Ltd.) of appropriate size (between size 1-1.5), depending on the weight of the patient, was introduced. Anaesthesia was maintained with 33% oxygen, 67% nitrous oxide and sevoflurane (3 -4%) with manual assistance and fresh gas flow of 2-3litres /minute.After induction of anaesthesia, the children were assigned randomly to receive a caudalepidural injection of either 0.75 ml.kg -1 of 0.25% bupivacaine (Group B) or 0.75 ml.kg -1 of 0.25% bupivacaine with 2µg.kg -1 of clonidine (Group C). Clonidine was loaded in 1ml syringe so as to keep the volume same in both thegroups. Caudalblockwas performed with 23 gauge hypodermic needle under aseptic conditions in left lateralposition and the child was turned supine after the injectionof thedrug. Mean blood pressure and heart rate were recorded before induction of anaesthesia and every 5 minutes subsequently. An intraoperative increase in heart rate and blood pressure by more than 10% after 15minutes of caudalinjection was defined as insufficient analgesia and treated with intravenous fentanyl 1mcg.kg -1 .
At the beginningof skin closure, sevoflurane and nitrous oxide were discontinued. When the children were sufficiently awake, PLMA was removed and they were shifted to the recovery room, breathingroom air.
After arrivalmean blood pressure, heart rate and SpO 2 was documented hourlyfor 6hours. Intraoperative or postoperative decrease in mean blood pressure or heart rate more than 30% of the baseline values was defined as severe hypotension or bradycardia respectively. Respiratory depression was defined as a decrease of SpO 2 less than 93% and required supplementaloxygen via mask. Pain assessment in the postoperative period was done by an observer blinded to the therapeutic intervention using OPS score (at 30 minutes, 1 hour and 2hours) and duration of analgesia. Each variable (crying,facial expression,verbalresponse, position of torso and motor restlessness) was scored between 0-2 (0: none, 1: moderate, 2: severe), to give a cumulative score of 0-10. If the OPS score was more than 4 in 2 subsequent measurements or if the patient showed obvious signs of pain they were given oral paracetamol 10 mg.kg -1 . The duration of postoperative analgesia was defined as time betweencaudal drug injection and the first complaint of pain.Assessment of sedation was done by sedation score at 30 minutes, 1hour and 4 hours after the operation. Patient sedation score was defined as 1: asleep, not arousable by verbalcontact; 2: asleep, arousable by verbal contact; 3: drowsy not sleeping; 4: alert/aware. This helped in identification of respiratory depression. Duration of motor blockwas assessed by notingthe time children began movingtheirlegs. Timeof firstmicturition wasalso noted. Children were discharged from the daycare ward after 6hours of arrival. Parents noted the total requirement of additional analgesia in first 24 hours after operation on a form and were contacted telephonically.
Parametric data was analysed using Student's t test.

Results
Mean age, weight, surgical and recovery time were comparable between two groups (mean age of Group B: 3.3 years, mean age of Group C: 3.5 years, mean weight of Group B: 13.5 kg, mean weight of Group C: 14.6kg, mean surgical time of Group B: 39.7 min, mean surgicaltime ofGroup C:43.8 min,as shown in Table 1). The duration of analgesia and the time for first postoperative analgesic requirement was significantly prolonged in Group C ( Table 2 & Fig1). There was a decrease from base line mean arterial pressure in Group C 5-15 minutes after the injection but it returned to normalin 30minutes. The mean time for first   Fig 1).
The comparison of mean arterialpressure during intraoperative and post operative period (Fig 2 & 3), between both groups, using Student'st test, yielded pvalues (0.86 for intraoperative MAP and 0.15for postoperative MAP) which were not significant. The comparison of heart rate during intraoperative and post operative period, between both groups showed insignificant p-value (p-value for intraoperative heart rate was 0.99and for postoperative heart rate it was 0.54). With N as 20 in each group with a mean prolongation of analgesia by 5.75 hours in Group C as compared to Group B (Fig 6), the power of study was 94.2% and the p-value less than 0.05 (p< 0.001).
Noneof the children hadurinary retention and the incidence of vomiting was comparable between the groups (Table1, 2). None of the childrenhad SpO 2 value less than 95%. None of the children had bradycardia. On awakeningno motorblockwas observed inany case in either group. There was no significant difference in either group in the mean postoperative sedation score (Group Bwas 2.8± 0.45and Group C was 2.83, (Table 2& Fig 4). The mean OPS score of Group Bwas 4.65 ± 0.25 and Group C was 4.55 ± 0.25 (Table 2 & Fig  5). Themean timeof firstmicturition inGroup Bwas 4.8 hours and in Group C was 4.7 hours.

Discussion
Our data indicates that for caudal blockade, the addition of clonidine 2 µg.kg -1 with 0.25%bupivacaine significantly prolongs the duration of analgesia (Table 2 & Fig 1). This reduces the need for both intraoperative and postoperative analgesia.These findingsconfirm with aprevious study 7 which reportedthat 1-2µgof clonidine with bupivacaineincreases duration of analgesiain small children undergoing day care hernia repair compared to bupivacaine alone or bupivacaine with epinephrine 5µg.ml -1 .
Duration of analgesia inthis study is lessthan that observed in another study 8 where they used combination of ketamine 1 mg.kg -1 and clonidine 1-2 µg.kg -1 of caudal blockade in children.
The undesirable sideeffects ofneuraxial clonidine are hypotension and bradycardia. Many studies 6,12,13 in adult patients have reported a decrease in MAP and HR within 15-30 minutesafter epiduralinjection which lasted for 3-4 hrs before returning to baseline. In our study decrease in blood pressure did occur in all patients who were givenclonidine withbupivacaine within 5-15minutes but returned tonormalwithin30 minutes.
Some studies 12,13 report amarked decreasein heart rate afterepidural clonidine while others do not.We did not observe any significant bradycardia inour study.
Dose dependentsedation usuallyaccompanies the use of clonidine for regional anaesthesia 6,14 , however with 2µg.kg -1 , we did not appreciate any excessive sedation (Fig 2 and 6).All the children were sleeping but arousable and this was appreciated by the parents.
All children could move their legs at the end of 6 hour period and there was no case of retentionof urine.
Except for 2 patients, there was no case of postoperative vomiting and therefore discharge of no child was delayed.
This studyused patients undergoing thesame surgicalprocedure, no premedication and samepattern of induction so as to eliminate any factor that could have interfered withanalgesia requirementor haemodynamic variables.
The use of parents to assess pain after discharge till24 hours may introduce some sort of inconsistency in deciding to medicate the child but it is the parents who know their child best.
The main purpose of our study was to assess the suitability of clonidine and bupivacaine in daycare patients who are to go home the same day. Absence of any side effect like sedation, bradycardia,vomiting and respiratory depression with reduction in the need of analgesic goes in the favor of usingclonidine as an adjuvant with localanaesthetic in this set of patients.
We chose dose of 2 µg.kg -1 as compared to 1µg.kg -1 as used inmany studies, as this dose provides benefit to the child with no additional risk of side effects. The text of original articles should be divided into sections with the headings: Summary, Key-words, Introduction, Methods, Results, Discussion, References, Tables and  Figure legends. For a brief report include Summary, Key-words, Introduction, Case report, Discussion, Reference, Tables and Legends in that order. Do not use subheadings in these sections. Use double spacing throughout. Number pages consecutively, beginning with the title page.